Knockdown of lncRNA H19 alleviates ox-LDL-induced HCAECs inflammation and injury by mediating miR-20a-5p/HDAC4 axis.

Autor: Yang Y; Department of Geriatrics, Changsha Third Hospital, No. 176, Laodong West Road, Tianxin District, Changsha, 410004, Hunan Province, People's Republic of China., Wang Z; Department of Cardiology, Changsha First Hospital, Changsha, 410010, Hunan Province, People's Republic of China., Xu Y; Department of Geriatrics, Changsha Third Hospital, No. 176, Laodong West Road, Tianxin District, Changsha, 410004, Hunan Province, People's Republic of China., Liu X; Department of Geriatrics, Changsha Third Hospital, No. 176, Laodong West Road, Tianxin District, Changsha, 410004, Hunan Province, People's Republic of China., Sun Y; Department of Geriatrics, Changsha Third Hospital, No. 176, Laodong West Road, Tianxin District, Changsha, 410004, Hunan Province, People's Republic of China., Li W; Department of Geriatrics, Changsha Third Hospital, No. 176, Laodong West Road, Tianxin District, Changsha, 410004, Hunan Province, People's Republic of China. lweregfe1013@163.com.
Jazyk: angličtina
Zdroj: Inflammation research : official journal of the European Histamine Research Society ... [et al.] [Inflamm Res] 2022 Sep; Vol. 71 (9), pp. 1109-1121. Date of Electronic Publication: 2022 Jul 19.
DOI: 10.1007/s00011-022-01604-z
Abstrakt: Background: Coronary artery disease (CAD) seriously disturbs the life of people. LncRNA H19 is reported to promote the progression of CAD; Nevertheless, the detailed mechanism by which H19 modulates CAD development is unclear.
Methods: Clinical samples of CAD patients were collected, meanwhile we established in vitro and in vivo models of CAD by treating HCAECs with ox-LDL and feeding ApoE -/- mice with high fat diets (HFD). MTT assay was adopted to assess the cell viability. Transwell detection was applied to test the migration, and apoptosis was tested by flow cytometry. The levels of inflammatory cytokines were examined by ELISA. The relation among H19, miR-20a-5p and HDAC4 was explored by dual luciferase reporter and RIP assay.
Results: H19 and HDAC4 levels were elevated, while miR-20a-5p was reduced in plasma of CAD patients and ox-LDL-treated HCAECs. ox-LDL increased H19 level and induced apoptosis and inflammation in HCAECs, while silencing of H19 rescued this phenomenon. In addition, the level of H19 was negatively correlated with miR-20a-5p, and miR-20a-5p inhibitor restored the effect of H19 silencing on HCAECs function. HDAC4 was the downstream mRNA of miR-20a-5p, and miR-20a-5p upregulation reversed ox-LDL-induced HCAECs injury through targeting HDAC4. Furthermore, H19 silencing significantly alleviated the coronary atherosclerotic plaques and inhibited the inflammatory responses in vivo.
Conclusions: We proved that knockdown of H19 alleviated ox-LDL-induced HCAECs injury via miR-20a-5p/HDAC4 axis, which might provide a new tactics against CAD.
(© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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